The gastrointestinal epithelium plays a central role in maintaining and coordinating mucosal homeostasis and immunity. Intestinal epithelial barrier compromise in mucosal wounds is seen in many pathologic states that encompass inflammatory bowel diseases, ischemia, mechanical injury and surgical procedures. Coordinated epithelial cell migration and proliferation required for wound closure is a complex process that is not well understood. Our overarching hypothesis is that epithelial and immune cell mediators in the intestinal mucosa coordinate epithelial repair responses. Thus, the proposed studies will identify and characterize mechanisms by which lipid and protein mediators in the intestinal mucosa promote wound repair. Knowledge gained from these studies in the short term will provide a better understanding of basic mechanisms by which inflammatory cell and epithelial mediators control intestinal epithelial homeostasis and mucosal wound repair. In the long term these studies will aid in the development of new therapeutic strategies aimed at promoting intestinal mucosal wound repair.